Auto ubiquitination of oligo-TRAF6 bound to p-IRAK2 at endosome membrane

Stable Identifier
R-HSA-975147
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
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Summation

TRAF6 possesses ubiquitin ligase activity and undergoes K-63-linked auto-ubiquitination after its oligomerization. In the first step, ubiquitin is activated by an E1 ubiquitin activating enzyme. The activated ubiquitin is transferred to a E2 conjugating enzyme (a heterodimer of proteins Ubc13 and Uev1A) forming the E2-Ub thioester. Finally, in the presence of ubiquitin-protein ligase E3 (TRAF6, a RING-domain E3), ubiquitin is attached to the target protein (TRAF6 on residue Lysine 124) through an isopeptide bond between the C-terminus of ubiquitin and the epsilon-amino group of a lysine residue in the target protein. In contrast to K-48-linked ubiquitination that leads to the proteosomal degradation of the target protein, K-63-linked polyubiquitin chains act as a scaffold to assemble protein kinase complexes and mediate their activation through proteosome-independent mechanisms. This K63 polyubiquitinated TRAF6 activates the TAK1 kinase complex.

Literature References
PubMed ID Title Journal Year
17135271 Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation

Lamothe, B, Besse, A, Campos, AD, Webster, WK, Wu, H, Darnay, BG

J Biol Chem 2007
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin-protein transferase activity of p-IRAK2:oligo-TRAF6 [endosome membrane]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed